Targeting Morphine

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Science  26 Nov 2004:
Vol. 306, Issue 5701, pp. 1441
DOI: 10.1126/science.306.5701.1441b

Gene silencing via RNA interference has rapidly become a widely used technique. Introducing RNA constructs complementary to endogenous messenger RNAs (mRNAs) leads to degradation of the mRNA transcripts and a decrease in the corresponding proteins. Allen et al. have applied this approach to the opium poppy Papaver somniferum with satisfying yet unpredicted results.

The enzyme codeinone reductase (COR) converts codeinone to codeine, which is demethylated to morphine. A hairpin RNA designed to target all seven members of the Cor gene family yielded transgenic plants displaying varying degrees of diminished morphine production, from 25 to 100%, along with the compensatory accumulation of the morphine precursor reticuline; this result was unexpected because reticuline lies eight steps upstream from morphine. The authors suggest that substrate compartmentalization or multienzyme complexes may explain this distant feedback inhibition. — GJC

Nature Biotechnol. 10.1038/nbt1033 (2004).

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